Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene

The polymorphism SNP309 (rs2279744) in the promoter region of the
MDM2 gene has been shown to alter protein expression and may play a
role in the susceptibility to lung cancer. The MDM2 protein is a
key inhibitor of p53 and several mechanisms of MDM2/p53
interactions are presently known: modulating DNA-repair, cell-cycle
control, cell growth and apoptosis. We used 635 Caucasian patients
diagnosed with lung cancer before 51 years of age and 1300 healthy
gender and age frequency matched population Caucasian controls to
investigate the association between the MDM2 SNP309 and the risk of
developing early onset lung cancer. Conditional logistic models
were applied to assess the genotype-phenotype association, adjusted
for smoking. Compared to the GG genotype, the adjusted ORs for the
TG and TT genotype were 0.9 (95% CI: 0.7-1.5) and 1.0 ( 95% CI:
0.7-1.5), respectively. Also no association was found for
histological subtypes of lung cancer. The strength of this study is
that within young cases the genetic component to develop lung
cancer may be greater. Our results indicate that the MDM2 SNP309 is
not significantly associated with lung carcinogenesis but point
towards gender-specific differences.